Green tea polyphenols alleviate early BBB damage during experimental focal cerebral ischemia through regulating tight junctions and PKCalpha signaling.
Green tea polyphenols alleviate early BBB damage during experimental focal cerebral ischemia through regulating tight junctions and PKCalpha signaling.
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绿茶多酚通过调节紧密连接和 PKCα 信号传导减轻实验性局灶性脑缺血期间的早期 BBB 损伤
DOI：
10.1186/1472-6882-13-187
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发表时间：
2013-07-21
影响因子：
--
通讯作者：
Xue Y
中科院分区：
文献类型：
--
作者：
Liu X;Wang Z;Wang P;Yu B;Liu Y;Xue Y
动物实验表明，绿色茶多酚（GTPs）对脑缺血后的脑损伤具有神经保护作用。关于GTP对缺血性卒中后血脑屏障（BBB）破坏的保护作用知之甚少。我们研究了GTP对claudin-5、occludin和ZO-1表达的影响，以及参与脑缺血早期的相应细胞机制。雄性Wistar大鼠进行大脑中动脉闭塞（MCAO）0，30，60，和120分钟。在MCAO之前，通过胃内管饲法每天两次给予GTP（400 mg/kg/天）或媒介物，持续30天。在不同时间点，检测缺血脑组织微血管碎片中claudin-5、occludin、ZO-1和PKCα信号通路的表达。与载体组相比，GTP在缺血后60分钟和120分钟降低BBB通透性。透射电子显微镜观察发现，GTP可逆转MACO后60 min和120 min紧密连接屏障的开放。在大鼠脑缺血后相同时间点用GTP处理可显著防止脑缺血组织微血管碎片中claudin-5、occludin和ZO-1的mRNA和蛋白表达水平的降低。此外，GTP还能抑制脑缺血引起的PKCα mRNA和蛋白表达水平的升高。提示GTP可能通过调节TJ和PKCα信号通路，对局灶性脑缺血早期BBB损伤具有潜在的神经保护作用。
It has been supposed that green tea polyphenols (GTPs) have neuroprotective effects on brain damage after brain ischemia in animal experiments. Little is known regarding GTPs’ protective effects against the blood-brain barrier (BBB) disruption after ischemic stroke. We investigated the effects of GTPs on the expression of claudin-5, occludin, and ZO-1, and the corresponding cellular mechanisms involved in the early stage of cerebral ischemia. Male Wistar rats were subjected to a middle cerebral artery occlusion (MCAO) for 0, 30, 60, and 120 min. GTPs (400 mg/kg/day) or vehicle was administered by intragastric gavage twice a day for 30 days prior to MCAO. At different time points, the expression of claudin-5, occludin, ZO-1, and PKCα signaling pathway in microvessel fragments of cerebral ischemic tissue were evaluated. GTPs reduced BBB permeability at 60 min and 120 min after ischemia as compared with the vehicle group. Transmission electron microscopy also revealed that GTPs could reverse the opening of tight junction (TJ) barrier at 60 min and 120 min after MACO. The decreased mRNA and protein expression levels of claudin-5, occludin, and ZO-1 in microvessel fragments of cerebral ischemic tissue were significantly prevented by treatment with GTPs at the same time points after ischemia in rats. Furthermore, GTPs could attenuate the increase in the expression levels of PKCα mRNA and protein caused by cerebral ischemia. These results demonstrate that GTPs may act as a potential neuroprotective agent against BBB damage at the early stage of focal cerebral ischemia through the regulation of TJ and PKCα signaling.
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影响因子：
4.2
作者：
Frei, B;Higdon, JV
通讯作者：
Higdon, JV
影响因子：
4.7
作者：
Ono, K;Yoshiike, Y;Yamada, M
通讯作者：
Yamada, M
影响因子：
2.9
作者：
Belayev, L;Busto, R;Ginsberg, MD
通讯作者：
Ginsberg, MD
影响因子：
4.2
作者：
Lee, H;Bae, JH;Lee, SR
通讯作者：
Lee, SR
影响因子：
2.4
作者：
Piao, Min-Sheng;Lee, Jung-Kil;Kim, Hyung-Seok
通讯作者：
Kim, Hyung-Seok